Metered dose inhalers (MDIs) are used to deliver a metered amount of an aerosolised drug directly to the patient's lung by inhalation. They are typically used to deliver drugs comprising bronchodilators (e.g. salbutamol) or corticosteroids (e.g. beclomethasone) for the treatment and control of asthma and Chronic Obstructive Pulmonary Disease (COPD).
The drugs are contained in an aluminium canister which is fitted at its open end with a metering valve. The stem of the metering valve is housed in a nozzle block within an actuator body, the actuator body having a mouth piece portion through which a patient can inhale. The valve is operated to release the metered dose of drug towards the mouth piece by depression of the canister within the actuator body.
In order to propel the drug from the canister in the form of an aerosol, a liquid propellant is contained within the canister along with the drug. The drug is then available for inhalation in the form of a fine mist with the drug dispersed in the high vapour pressure propellant.
A propellant must meet certain criteria. It must be a chemically stable liquefied gas having low toxicity and low flammability. It must be acceptable to patients in terms of taste and smell and it must have appropriate solvency characteristics to allow for drug formulation.
The drug/propellant formulation may either be a suspension formulation with the micro-particulate drug suspended within the propellant or a solution formulation with the drug dissolved in the propellant or in a combination of the propellant and a co-solvent such as ethanol.
Another important consideration in the choosing a propellant is that the vapour pressure must remain constant in order to ensure consistent dosing of the drug.
The earliest MDIs used chlorofluorocarbon (CFC) propellants which have since been phased out and replaced with hydrofluorocarbons (HFCs) due to the undesirable impact on the environment associated with CFC use. Both CFCs and HFCs form a two-phase (liquid and saturated vapour) system within the canister and a dynamic equilibrium exists between the two phases giving a constant vapour pressure irrespective of whether the canister is full or nearly empty. Propellants such as compressed carbon dioxide have previously been ruled out because the pressure would decrease as doses of the drug were emitted. This would lead to an inconsistent dose being delivered to the patient.
Continued use of HFCs as MDI propellants is undesirable since HFCs also have an undesirable environmental impact (albeit less than the impact of CFCs).
Accordingly, there is a desire to reduce the environmental impact of MDI use, especially as MDI use is predicted to increase.